Pediatric Bacterial Meningitis: An Update on Early Identification and Management (Pharmacology CME)

Pediatric Bacterial Meningitis: An Update on Early Identification and Management (Pharmacology CME)

Since bacterial meningitis can present with many signs and symptoms, differentiation of bacterial meningitis from viral meningitis and from other mimics can be difficult. If the presentation is not “classic” in nature, diagnostic and therapeutic delay can occur, frequently with devastating consequences. This issue provides evidence-based recommendations for the early identification and appropriate management of bacterial meningitis in pediatric patients. You will learn:

• The most common causative pathogens, based on patient age
• Typical clinical findings that are consistent with bacterial meningitis and how they vary for patients in different age groups
• Which physical examination findings indicate that a patient should undergo lumbar puncture
• Inflammatory markers in the serum and cerebrospinal fluid, such as procalcitonin, can help detect serious bacterial illness
• How clinical prediction scores, such as the bacterial meningitis score, can help distinguish between bacterial meningitis and viral meningitis
• Which antibiotic are recommended, and when they should be started
• The potential benefits of adjunct therapies, such as corticosteroids, and when they are indicated

Abstract

The presentation of bacterial meningitis can overlap with viral meningitis and other conditions, and emergency clinicians must remain vigilant to avoid delaying treatment for a child with bacterial meningitis. Inflammatory markers, such as procalcitonin, in the serum and cerebrospinal fluid may help distinguish between bacterial meningitis and viral meningitis. Appropriate early antibiotic treatment and management for bacterial meningitis is critical for optimal outcomes. Although debated, corticosteroids should be considered in certain cases. This issue provides evidence-based recommendations for the early identification and appropriate management of bacterial meningitis in pediatric patients.

Case Presentations

On a warm day in June, an unvaccinated 9-year-old girl is sent to your ED. Earlier that day, she was seen at her primary care physician’s office by a physician assistant who reported that the child had headache and fever intermittently for 3 to 4 days. The PA was concerned that she might have meningitis. The patient arrives, ambulatory and alert, complaining of a bitemporal headache. Her fever at home was 38.3°C (101°F). There has been no photophobia or rash, and there are no ill contacts. The child took acetaminophen 2 hours prior to arrival. On physical examination, the child is tired but not toxic-appearing. She had an episode of vomiting in triage. Her vital signs are: temperature, 38.7°C (101.6°F); heart rate, 142 beats/min; respiratory rate, 22 breaths/min; blood pressure, 119/77 mm Hg; and oxygen saturation, 95% on room air. Her pain score is 8/10. Her physical examination is notable for head and neck discomfort when moving from sitting to the supine position. Her neck has full range of motion and she is negative for Kernig sign and Brudzinski sign. The remainder of her examination is normal. The patient is given a 20 mL/kg normal saline bolus IV, 6 mg ondansetron IV, and 10 mg/kg ibuprofen orally. An hour later, her vital signs are: temperature, 37.2°C (99°F); heart rate, 126 beats/min; respiratory rate, 20 breaths/min; and blood pressure 111/67 mm Hg. Her pain score is now 4/10. Her peripheral white blood cell count is 16,000 with a left shift, and her chemistry is notable only for a glucose level of 146 mg/dL. Given the girl’s lack of frank meningismus and improvement with ibuprofen, is a lumbar puncture indicated? What are the most common causes of meningitis in this age group? Should antibiotics be given?

A 4-month-old boy presents with a history of cough, pallor, fever to 38.9°C (102°F), and decreased feeding on the morning of presentation. The infant drank 6 ounces about 4 hours before arrival, but would not feed at presentation. The boy’s parents state he did not vomit or have diarrhea. His past medical history is notable for cesarean delivery at 36 weeks' gestation. There was prolonged rupture of membranes and he was hospitalized for 3 days after delivery. The boy’s parents report no prior illnesses, and his immunizations are up-to-date. On physical examination, the boy’s vital signs are: temperature, 38.9°C (99.6°F); heart rate, 158 beats/min; respiratory rate, 50 breaths/min; and oxygen saturation, 98% on room air. The boy is arousable but sleepy and does not fix and follow. His fontanel is flat. His HEENT examination is notable for nasal congestion with mucus secretions. The boy’s cardiopulmonary and abdominal examinations are unremarkable. The boy’s capillary refill is < 2 seconds, but his muscle tone is decreased. He is fussy during the examination. Is this merely an upper respiratory infection or should meningitis be considered? What are common clinical features of meningitis in this age group? What further management is indicated? Which empiric antibiotics—if any—are indicated at this time?

Introduction

Bacterial meningitis in children is one of the most high-risk diagnostic and management challenges for the emergency clinician. Widespread implementation of vaccination strategies against pneumococcal, meningococcal, and Haemophilus influenzae type b diseases has led to a dramatic decline in the frequency of this condition over the past 3 decades.1,2 In some ways, however, this has made the early identification of bacterial meningitis more difficult for the emergency clinician. The rare occurrence of the condition means that a high-volume pediatric emergency clinician may evaluate only 1 child with bacterial meningitis every 3 to 5 years. Since bacterial meningitis can present with many signs and symptoms, differentiation of bacterial meningitis from viral meningitis and from other mimics can be difficult. If the presentation is not “classic” in nature, diagnostic and therapeutic delay can occur, frequently with devastating consequences. Inflammatory markers in the serum and cerebrospinal fluid, such as procalcitonin, may help distinguish between bacterial meningitis and viral meningitis. Children with suspected bacterial meningitis should be treated early and aggressively. Adjunct therapies such as corticosteroids are still highly debated but may be indicated in select cases. Until better diagnostic tools and therapies are established, emergency clinicians must remain vigilant to avoid treatment delays for a child with bacterial meningitis.

This issue of Pediatric Emergency Medicine Practice reviews the classic clinical findings associated with bacterial meningitis, offers guidance for using studies and scoring systems to aid in the diagnosis of bacterial meningitis, and provides evidence-based recommendations for the management of patients with bacterial meningitis.

Critical Appraisal of the Literature

A literature search was performed in PubMed and the Cochrane Database of Systematic Reviews using the search terms: pediatric bacterial meningitis, viral meningitis, pediatric lumbar puncture, neonatal fever, antibiotics for pediatric meningitis, and pediatric meningitis diagnostic studies. A total of 98 articles published between 1992 and 2018 were reviewed.

Risk Management Pitfalls in the Management of Pediatric Patients With Bacterial Meningitis

2. “The patient has inflamed tympanic membranes. The fever and irritability are likely due to otitis media. It’s not meningitis.”

Many young children with bacterial meningitis can have concomitant inflammation in other areas on physical examination or diagnostic study. Otitis media and upper respiratory tract infections are common enough conditions that their presence can lead the emergency clinician to “explain away” the child’s more serious symptoms as being due to those pathophysiologic findings. Anchoring on a simpler, less severe diagnosis can result in missing or delaying the correct diagnosis.

6. “The patient likely has viral meningitis, so we don't need to get a lumbar puncture.”

The notion that emergency clinicians can distinguish the difference between viral and bacterial meningitis based on the history and physical examination is not supported by the available evidence. The clinical overlap of these conditions is substantial, particularly early in the course of illness. Diagnosis should not be made based on the history and physical examination alone.

8. “We need to wait for a CT scan and lumbar puncture before we can give antibiotics, as they can cause sterilization of CSF.”

When caring for a patient with a presumptive diagnosis of bacterial meningitis, do not delay administration of appropriate antibiotics for the completion of a CT scan or lumbar puncture or for the results of these studies. Although antibiotics may obscure the ultimate bacteriologic diagnosis, this is a small clinical price to pay to prevent further bacterial proliferation and inflammation within the CNS.

Tables

References

Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of patients. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.

To help the reader judge the strength of each reference, pertinent information about the study is included in bold type following the reference, where available. In addition, the most informative references cited in this paper, as determined by the author, are highlighted.

Although the overall incidence of pediatric bacterial meningitis in the United States has decreased, the prevalence of non–PCV-13 pneumococcal serotypes and late-onset (6-90 days) and very-late-onset (> 90 days) group B Streptococcus meningitis has increased.

While the presence of the most widely recognized signs of bacterial meningitis—fever, bulging fontanel, meningismus, altered mental status, headache, and vomiting—significantly increases the likelihood of bacterial meningitis, a number of cases have been published in which these signs were absent.

The sensitivity of neck findings ranges from 45% to 95%. The sensitivity of assessing the range of motion in the sagittal plane may be enhanced by performing the test with the child sitting on the bed with legs outstretched rather than with the legs over the edge of the bed.

Introduction

The bacterial meningitis score for children rules out bacterial meningitis in pediatric patients with suspected meningitis.

Points & Pearls

The bacterial meningitis score (BMS) predicts bacterial versus aseptic etiology of meningitis in patients aged 29 days to 19 years with suspected meningitis.

The BMS can help determine if the patient will require admission for parenteral antibiotics while awaiting cerebrospinal fluid (CSF) culture results.

A higher BMS indicates a higher likelihood of bacterial meningitis.

Although the score was derived and validated in a population of children aged 29 days to 19 years, the sensitivity, specificity, and negative predictive value (NPV) of the BMS decrease significantly for children aged < 2 months. Therefore, the creators of the BMS advise against using it for children who are aged < 2 months, as well as for children who have already received antibiotics prior to the lumbar puncture, are ill-appearing, or have examination findings that are indicative of an invasive bacterial infection (eg, petechiae and purpura).

The BMS is not effective at ruling out potentially harmful nervous system infections (eg, herpes encephalitis, Lyme meningitis, tuberculous meningitis) that would require antibiotics.

Meningococcal meningitis can present without CSF pleocytosis; thus, patients with meningococcal meningitis could be misclassified as not having inclusion criteria for use of the BMS. It is important to perform a thorough physical examination to assess for petechiae or purpura if there is suspicion for meningococcemia or meningococcal meningitis, as the CSF culture may have a false normal result in these cases.

Why and When to Use, and Next Steps

Why to Use

The incidence of bacterial meningitis has dramatically declined since the advent of highly effective vaccines against some of the more common causes (eg, Haemophilus influenzae type b, Streptococcus pneumoniae). This has made it more challenging to determine which patients should be admitted for observation while awaiting CSF culture results.

The BMS helps identify patients who do not necessarily require observation due to the higher likelihood that they have aseptic (ie, spontaneously resolving) meningitis. It also helps avoid the financial burden and health risk that are associated with hospitalization for observation and administration of parenteral antibiotics.

When to Use

The BMS can be used in pediatric patients aged 29 days to 19 years with suspected meningitis.

Do NOT use the BMS if the patient:

Is critically ill, requiring respiratory or vasopressor support

Received antibiotics < 72 hours prior to the lumbar puncture

Has a ventriculoperitoneal shunt or has recently had neurosurgery

Is immunosuppressed

Has proof of another bacterial infection (eg, urinary tract infection, bone infection, or known bacteremia) that warrants inpatient antibiotic therapy

Has known active Lyme disease

Next Steps

For patients at very low risk for bacterial meningitis (BMS = 0):

Consider discharging the patient with close follow-up (ideally within 24-48 hours) and return precautions explained to the caregiver, including new seizure activity, altered mental status, purpuric rash, or other concerning symptoms.

Patients may have received a dose of empiric antibiotics after a lumbar puncture was performed if there is concern for bacterial meningitis. If no antibiotics were administered, consider giving a single dose of a long-acting antibiotic with good CSF penetration (eg, ceftriaxone) prior to discharge.

For patients with at least 1 risk factor or high clinical suspicion for bacterial meningitis (BMS > 0):

Consider admitting the patient for observation and administration of parenteral antibiotics while awaiting CSF culture results.

Calculator Review Author

Cullen Clark, MD

Departments of Emergency Medicine and Pediatrics

Louisiana State University Health Sciences Center

New Orleans, LA

Critical Actions

The clinician’s gestalt and the patient’s severity of illness and clinical presentation supersede the application of the BMS. If there is significant suspicion for bacterial meningitis, clinicians should err on the side of caution and admit the patient for observation and empiric antibiotics.

Instructions

The BMS should be used in patients aged 29 days to 19 years who have a CSF white blood cell count of ≥ 10 cells/μL. Do not use the BMS if the patient is critically ill, has recently received antibiotics, has a ventriculoperitoneal shunt or has recently had neurosurgery, is immunosuppressed, or has another bacterial infection that requires antibiotics (including Lyme disease).

Evidence Appraisal

The original BMS was derived from a multicenter retrospective cohort study published by Nigrovic et al in 2007. Data were collected from 20 participating emergency departments at academic medical centers over a 3-year period. The study used the BMS to classify 3295 patients aged 29 days to 19 years who had CSF pleocytosis. Among the 1714 patients who were categorized as very low risk, 2 were found to have bacterial meningitis. Both of the miscategorized patients were aged < 2 months and had E coli meningitis with an E coli urinary tract infection but a negative urinalysis. The sensitivity of the BMS for bacterial meningitis was 98.3% (95% confidence interval [CI], 94.2%-99.8%) and the NPV was 99.9% (95% CI, 99.6%-100%). The investigators attempted to refine the score using recursive partitioning, which led to a simpler model with only 3 variables, but also led to 1 additional patient with meningitis being misclassified as very low risk.

Given that the 2 misclassified patients were aged < 2 months, the investigators analyzed the BMS for a subgroup of all patients aged < 2 months and found that the sensitivity was 92.3% (95% CI, 74.9%-99.4%) and the NPV was 99.5% (95% CI, 98.3%-99.9%). The BMS was validated by Nigrovic et al in 2012, in a meta-analysis of studies published between 2002 and 2012 that included 4896 patients aged 29 days to 19 years. The sensitivity for bacterial meningitis was 99.3% (95% CI, 98.7%-99.7%) and the NPV was 98.3% (95% CI, 96.6%-99.3%).

In 2013, Kulik et al published a systematic review of several bacterial meningitis predictive rules. Among the studies reviewed, the authors found that the BMS had the highest quality of evidence and the best performance to date, but they still recommended that the score be further evaluated with prospective trials.

Nigrovic LE, Kuppermann N, Malley R. Development and validation of a multivariate predictive model to distinguish bacterial from aseptic meningitis in children in the post-Haemophilus influenza era. Pediatrics. 2002;110(4):712-719. https://www.ncbi.nlm.nih.gov/pubmed/12359784

CME Information

Identify the populations that are at high risk for bacterial meningitis

Recognize the variable clinical presentations of patients with bacterial meningitis

Discuss the challenges in making a prompt diagnosis

Diagnose and manage patients with bacterial meningitis.

CME Information

Date of Original Release: November 1, 2018. Date of most recent review: October 15, 2018. Termination date: November 1, 2021.

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